Activated human platelet products induce proarrhythmic effects in ventricular myocytes

Sudden cardiac death remains one of the most prevalent modes of death and is mainly caused by ventricular fibrillation (VF) in the setting of acute ischemia resulting from coronary thrombi. Animal experiments have shown that platelet activation may increase susceptibility of ischemic myocardium to VF, but the mechanism is unknown. In the present study, we evaluated the effects of activated blood platelet products (ABPPs) on electrophysiological properties and intracellular Ca2+ (Ca2+i) homeostasis. Platelets were collected from healthy volunteers. After activation, their secreted ABPPs were added to superfusion solutions. Rabbit ventricular myocytes were freshly isolated, and membrane potentials and Ca2+i were recorded using patch-clamp methodology and indo-1 fluorescence measurements, respectively. ABPPs prolonged action potential duration and induced early and delayed afterdepolarizations. ABPPs increased L-type Ca2+ current (ICa,L) density, but left densities of sodium current, inward rectifier K+ current, transient outward K+ current, and rapid component of the delayed rectifier K+ current unchanged. ABPPs did not affect kinetics or (in)activation properties of membrane currents. ABPPs increased systolic Ca2+i, Ca2+i transient amplitude, and sarcoplasmic reticulum Ca2+ content. ABPPs did not affect the Na+− Ca2+ exchange current (INCX) in Ca2+-buffered conditions. Products secreted from activated human platelets induce changes in ICa,L and Ca2+i, which result in action potential prolongation and the occurrence of early and delayed afterdepolarizations in rabbit myocytes. These changes may trigger and support reentrant arrhythmias in ischemia models of coronary thrombosis.

► Sudden cardiac death often results from coronary platelet aggregation.
► We examined effects of activated human blood platelet products on rabbit cardiomyocytes.
► Intracellular Ca2+ increased and action potentials prolonged.
► Early and delayed afterdepolarizations occurred.
► Activated human blood platelets release arrhythmic products.